The primate placenta utilizes maternal low density lipoproteins (LDL) as the preferred source of cholesterol for progesterone production. In the baboon, we have suggested that relative levels of cholesterol supplied to the syncytiotrophoblast via the LDL receptor (LDLr) and by de novo synthesis change in respect to LDL availability. We have also reported a developmental increase in LDL uptake with advancing gestation. Therefore, we now determine the relative abundances of placental messenger RNA (mRNA) transcripts for cholesterol-sensitive mechanisms at early (day 60, n=3), mid (day 100, n=4) and late (day 160, n=4) pregnancy by RT-PCR. Placentae were collected at cesarean section and villous tissue sampled. An enriched fraction of syncytiotrophoblast cells was also sequestered following enzymatic dispersion. Relative levels for LDLr, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, scavenger" receptor types I and II (Sc I/II) and LDL receptor-related protein (LRP) transcripts were determined in respect to constitutively expressed glyceraldehyde-3-phosphate dehydrogenase. In whole villous tissue there were no differences (P>0.05) in mRNA levels for LDLr, HMG-CoA reductase, LRP, Sc I or Sc II in respect to gestational age. In syncytiotrophoblast, however, relative densities (mean+SEM) of PCR products for LDLr were 0.26+0.05, 0.77+0.14, 0.82+0.18, for HMG-CoA reductase were 0.26+0.01, 0.60+0.21, 0.61+0.25, for early, mid and late pregnancy, respectively. Thus, LDLr and HMG-CoA reductase mRNA levels were higher (P<0.05) in syncytiotrophoblast from mid and late pregnancy than from early. Although no significant change in Sc II mRNA abundance occurred with advancing gestation, expression was approximately two-fold higher (P<0.05) in syncytiotroblast than in villous tissue. Transcripts for Sc I and LRP were not apparent in syncytiotrophoblast. Thus, HMG-CoA reductase mRNA was enhanced in syncytiotrophoblast with advancing baboon gestation. Disparities in HMG-CoA reductase and Sc II transcript abundance imply a further divergence in pathways regulating cholesterol homeostasis in steroidogenically active syncytiotrophoblasts